The objectives of the proposed research are: (1) to obtain a description of the ribonucleases of normal human serum and urine, including the number of species present, their electrophoretic properties, concentration, and catalytic properties; (2) determine whether the elevated serum ribonuclease activity associated with various diseases, especially cancer, is due to high levels of an enzyme(s) normally present in serum and urine or whether abnormal species are present; correlating of serum ribonuclease patterns with the histology and anatomical site of the primary tumor will be sought; (3) to determine which, if any, of the ribonucleases present in serum might originate in the formed elements of the blood; (4) to ascertain whether a carefully designed assay protocol will improve the reliability of elevated serum and/or urine ribonuclease activity as an indicator of specific malignant diseases in addition to multiple myeloma; (5) to develop low molecular weight, synthetic ribonuclease substrates which upon enzymatic cleavage release a chromophore, or products reacting readily to give chromophores; such substrates, unlike the polynucleotides commonly employed, would be well suited for routine use in clinical laboratories; (6) to test the low molecular weight synthetic substrates, which would include esters of each of the four common ribonucleotides, as reagents for assay of total serum and urine ribonuclease activity and as potential indicators of elevation of particular, constituent RNase species having pronounced base preference.